Darr House is able to offer its client’s completely flexible arrangements whereby synthetic projects whether large or small can be entertained and the following objectives can be fulfilled to the client’s exact requirements:
- Lead identification, route engineering and optimisation.
- Scale-up of intermediates and/or leads.
- Timescale adherence.
- Full analytical support
- Confidentiality and IP: Darr House CDA available.
- Exclusivity as required.
- Full time equivalency, daily/hourly rates or pro rata.
- Weekly progress reports to teh customer available on request.
- Fast lead times.
Darr House is able to provide milligramme to multigramme chemistry to exact client specification or route engineering as required.
- Fast lead times
- Full analytical support: NMR (1H/13C/19F/31P) LC/MS HPLC (including preparative) Elemental analysis (C/H/N/O/S)
We are able to offer considerable experience and knowledge in organic synthesis whether geared to aromatic, aliphatic or heterocyclic chemistry but also specialisation in organofluorine chemistry and peptide synthesis. In addition, considerable expertise in organometallic synthesis is at hand. We also have extensive experience in lead identification and optimisation whether aimed at pharma or agrochem synthesis programmes. This makes us an ideal choice for contract synthesis of target entities and/or intermediates and small library production.
Darr House is able to provide its clients with further insight into their desired chemistries utilising state-of-the-art molecular modelling software, namely Hyperchem™ and Spartan™. Therefore prediction of chemical behaviour and/or properties can be provided e.g. determination of equilibrium and/or transition state geometries/conformational analysis, HOMO/LUMO energy determination coupled with database access to >150,000 organic compounds for comparison. In addition, prediction of medicinal chemistry characteristics can be entertained, e.g. LogP, PSA, ESP determination and pharmacophore identification using similarity analysis for example are available in-house.
The 3-chloro-5-(trifluoromethyl)pyridinyl (3,5-CTFP) moiety has a proven track record as a "biophilic agrophore" in crop protection across all the three main pesticide classes.1 Notable examples of successful crop protection agents that contain this moiety include Chlorfluazuron (Insecticide:Benzoyl phenylurea class/ISK), Haloxyfop-methyl (Hebicide: Ayloxyphenoxypropionic acid class/Dow Agrosciences), Fluazinam (Fungicide: Anilinopyridine class/ISK). Remarkably, new commercial products continue to be discovered that contain this moiety. In 2006, Bayer Cropscience launched Fluopicolide a fungicide with a new mode action and first in acyl picolide class.1 As recently as 2010/2011 Bayer Cropscience launched Fluopyram a Complex II/Succinate Dehydrogenase Inhibitor and first ethyl benzamide class.2 Structurally, very similar to Fluopicolide and yet with a completely different mode of action. These observations reinforce the remarkable ability of the 3,5-CTFP to impart successful biological activity in the crop protection arena.
Partly, this can be explained by the presence of the trifluoromethyl group, which has, and in conjunction with other forms of introduction of the element Fluorine been known to increase the lipophilicity of molecules and thereby assisting in transportation across cell membranes so that the active site may more easily be attained. In fact, the number of commercial crop protection agents containing Fluorine alone or as in part of some other functional group is astounding.
Recognising the importance of the 3,5-CTFP moiety and the virtue of Fluorine introduction into crop protection research, Darr House began to undertake research into new intermediates for crop protection research. Specifically, we have been interested in the introduction of the gem-difluoromethylene moiety. This moiety has significant relevance in the search for biologically active molecules, e.g. as a bioisostere for the the ether group, the ability to modulate the acidity of adjacent funcionality and the inhibition of biological oxidation. These attributes have been exploited commercially in the pharmaceutical arena with the launch of successful drugs, e.g. the antineoplastic, Gemcitabine. Interestingly, and somewhat surprisingly there exist no crop protection agent that contains this moiety to date. We have recognised the key importance that these attributes can bring to crop protection research and have combined them to create a series of unique intermediates, which will offer the crop protection chemist entry into whole new world of previously inacessible substitution patterns. We feel this will further strengthten the argument for the "Agrophore-based" approach to the discovery of new crop protection agents and it is our firm belief that in the not too distant future a crop protection agent will be realised, which contains both these moieties.References:
- 1. Briggs, G. et al., Pflanzenschutz-Nachrichten Bayer, 59, 141-152 (2006).
- 2. Rieck, H., Coqueron, P-Y., Modern Crop Protection Agents 2nd Ed, Vol 2, 15.3.2, 639, (2012).